The objectives are to ascertain the structural basis of nephron filtration in normal and nephrotic animal models that mimic human renal diseases. To achieve these objectives, an array of ultrastructural and immunological tracers will be employed to ascertain the structural pathways and barriers of glomerular and tubular filtration in hopes that an understanding of proteinuria in human renal disease will be forthcoming. In addition, scanning and immunocytochemical studies will be utilized to elucidate glomerular morphology and study the histochemistry of the glomerular tuft, with emphasis on the role the visceral epithelial cells play in filtration respectively. Furthermore, a quantitative study of proteinuria in all the above animal models will be correlated with nephron filtration results. In situ and in vitro renal perfusions with protein tracers as well as defining glomerular physiology and ultrastructure during oxygenated perfusates with anti-metabolites will be correlated with filtration data and with findings on the slit diaphragm, GBM and podocyte changes.